1. Field of the Invention
This invention relates to a method and apparatus for collecting interstitial fluid and analyzing same for the presence of an analyte. More particularly, the analyte is glucose.
2. Discussion of the Art
The prevalence of diabetes has been increasing markedly in the world. At this time, diagnosed diabetics represented about 3% of the population of the United States. It is believed that the total actual number of diabetics in the United States is over 16,000,000. Diabetes can lead to numerous complications, such as, for example, retinopathy, nephropathy, and neuropathy.
The most important factor for reducing diabetes-associated complications is the maintenance of an appropriate level of glucose in the blood stream. The maintenance of the appropriate level of glucose in the blood stream may prevent and even reverse many of the effects of diabetes.
Glucose monitoring devices of the prior art have operated on the principle of taking blood from an individual by a variety of methods, such as by needle or lance. An individual then coats a paper strip carrying chemistry with the blood, and finally insert the blood-coated strip into a blood glucose meter for measurement of glucose concentration by determination of change in reflectance.
The medical apparatus of the prior art for monitoring the level of glucose in the blood stream required that an individual have separately available a needle or lancet for extracting blood from the individual, strips carrying blood chemistry for creating a chemical reaction with respect to the glucose in the blood stream and changing color, and a blood glucose meter for reading the change in color indicating the level of glucose in the blood stream. The level of blood glucose, when measured by a glucose meter, is read from a strip carrying the blood chemistry through the well-known process of reading reflectometers for glucose oxidation.
Generally lancets comprise a blade and a pressable end opposed thereto, with the blade having an acute end capable of being thrust into skin of a human. By striking the pressable portion, the acute end of the blade will pierce the skin, for example, of the finger. The finger lancet is primarily used to obtain small volumes of blood, i.e., less than 1 mL. Diabetics use the finger lancet to obtain volumes of blood less than 25 xcexcL for analysis for glucose. A small amount of blood for the blood test will ooze out of the skin. There are many small blood vessels in each finger so that a finger can be squeezed to cause a larger drop of blood to ooze. The finger is one of the most sensitive parts of the body; accordingly, the finger lancet leads to even more pain than what would be experienced by extracting blood via lancet at a different body site. The finger lancet presents another problem because of the limited area available on the fingers for lancing. Because diabetics typically monitor their blood glucose levels two to four times per day, the limited area on the fingers calls for repeated lancing of areas that are already sore. Because fingers are sensitive to pain, it is a recent tendency that the arm is subjected to blood sampling. See, for example, U.S. Pat. No. 4,653,513. The device of U.S. Pat. No. 4,653,513 comprises a cylindrical housing and a lancet support, which has a gasket or flexible portion slidably accommodated in the housing. Springs will retract the lancet support to thereby reduce air pressure in the housing so that it sucks a blood sample, automatically and immediately after a lancet pierces the skin.
Because the blood volume requirements for a standard glucose test strip is typically 3 xcexcL or more, an area of the body that can generate that much blood from a lancet wound must be used. It is believed, however, that improvements in glucose test strip technology will reduce the volume of blood needed to 1 to 3 xcexcL. Because the finger is well supplied with blood and the amount of blood can be increased by squeezing the finger after lancing, the finger is the currently preferred body site for lancing, even though lancing of the finger is painful.
A less painful technique for obtaining body fluids could be found if a reliable method were found for lancing a body part that is less sensitive to pain than the finger and obtaining a useful amount of blood from that body part. A body part such as the forearm is much less sensitive to pain than the finger, but the amount of blood resulting from the lancing procedure is generally of an inadequate volume for use with current detection technology. Ways of increasing blood flow to the finger are common knowledge. The recommendation is made to diabetics to run their finger under hot water prior to lancing to improve the blood flow in the finger and the amount of blood collected from the lancet. Running hot water over a body part to improve blood flow is impractical for areas such as the forearm or thigh. The availability of hot water is also a concern. It would be desirable to develop a technique and apparatus for obtaining blood for diagnostic purposes in a painless, reliable manner.
Several patents have proposed that the level of glucose in blood can be monitored by measuring the level of glucose in interstitial fluid. In order to obtain samples of interstitial fluid, the barrier function of the stratum corneum must be overcome. Jacques, U.S. Pat. No. 4,775,361, discloses a method of ablating the stratum corneum of a region of the skin of a patient by using pulsed laser light of a wavelength, pulse length, pulse energy, pulse number, and pulse repetition rate sufficient to ablate the stratum corneum without significantly damaging the underlying epidermis. This patent discloses the use of laser light having a wavelength of 193 nm or 2940 nm. Laser light having wavelengths of 193 nm or 2940 nm can be provided by an excimer or Er:YAG light source, respectively, both of which are extremely expensive.
Tankovich, U.S. Pat. No. 5,423,803, discloses a process for the removal of superficial epidermal skin cells, i.e., stratum corneum, in the human skin. A contaminant having a high absorption in at least one wavelength of light is topically applied to the surface of the skin. Some of the contaminant is forced to infiltrate into spaces between superficial epidermal cells. The skin section is illuminated with short laser pulses at the above wave-length, with at least one of the pulses having sufficient energy to cause some of the particles to explode tearing off the superficial epidermal cells. In a preferred embodiment, the contaminant includes 1 micron graphite particles and the laser used is a Nd:YAG laser.
Zahrov, WO 94/09713, discloses a method for perforating skin comprising the steps of (a) focusing a laser beam in the shape of an ellipse at the surface of the skin with sufficient energy density to create a hole at least as deep as the keratin layer and at most as deep as the capillary layer; and (b) creating at least one hole, each hole having a width between 0.05 and 0.5 mm and a length of equal to or less than 2.5 mm. This patent discloses a variety of lasers suitable for carrying out this method. However, the method disclosed in Zahrov is limited to light source having a wavelength of 2940 nm. As stated previously, laser light of this wavelength can be provided by a Er:YAG light source, which is very expensive. Moreover, such a light source is relatively large, with the result that it would not be practical for use in a hand-held device.
It would be desirable to provide a method for providing an opening in the surface of the skin wherein an inexpensive light source is utilized, wherein the light source is of a size small enough to be portable and holdable in the hand of the user.
This invention provides an article capable of both collecting interstitial fluid and detecting an analyte in that fluid. Preferably, the article is also capable of measuring the amount of analyte in the interstitial fluid. The article can be used in conjunction with a meter that contains an appropriate detection element for determining the amount of analyte in the interstitial fluid. In one preferred embodiment, the article is a multiple-layer element comprising:
(1) a layer that is capable of being placed in contact with the skin of a patient;
(2) an overcoat layer that is coated over the skin-contacting layer;
(3) a layer, substantially coplanar with the overcoat layer, that is capable of transporting interstitial fluid by means of chemically aided wicking;
(4) a layer, overlying the interstitial fluid transporting layer, that is capable of being placed in contact with a meter, which layer has an opening therein through which light can be transmitted;
(5) a layer in communication with the interstitial fluid transporting layer, which layer is capable of detecting the presence of analyte or measuring the amount of analyte in the interstitial fluid.
In order to use the multiple-layer element, light from a source of light is transmitted through the opening in the multiple-layer material to be absorbed at a light-absorbing target on the skin-contacting layer. This light transfers energy to the target, and this transferred energy causes an opening to form in the skin-contacting layer and an opening to form in the stratum corneum. Interstitial fluid exudes from the opening in the stratum corneum and contacts the interstitial fluid transporting layer. The interstitial fluid then moves along or through the interstitial fluid transporting layer to the detecting layer. Preferably, the detecting layer comprises an electrochemical sensor or an optical sensor.
The multiple-layer element integrates the light-absorbing target, the skin-contacting layer, the overcoat layer, the fluid-transporting layer, the meter-contacting layer, and the detecting layer into one element. This integrated element can be made at a low enough cost to be disposable.
The collection of the interstitial fluid by this invention is less painful than is collection initiated by lancing with a conventional lancet. The patient is not required to handle the interstitial fluid. Consequently, sample placement errors are greatly reduced. Furthermore, a smaller sample of interstitial fluid is needed because no fluid is spilled during transfer of the fluid to a detector.